Myeloproliferative neoplasms and thrombosis by Tiziano Barbui, Guido Finazzi, and Anna Falanga Blood Volume 122(13):2176-2184 September 26, 2013 ©2013 by American Society of Hematology

Pathogenesis of thrombophilia in MPN Pathogenesis of thrombophilia in MPN. The pathogenesis of the acquired thrombophilic state in ET and PV is multifaceted. Pathogenesis of thrombophilia in MPN. The pathogenesis of the acquired thrombophilic state in ET and PV is multifaceted. Mechanisms involved in the pathogenesis of the acquired thrombophilic state associated with these diseases include abnormalities of MPN-clone–derived blood cells (ie, erythrocytes, platelets, and leukocytes), which display prothrombotic features, and abnormalities of normal vascular cells, which become procoagulant in response to inflammatory stimuli. Once activated, neutrophils can also affect the hemostatic system through different pathways. In particular, the release of proteolytic enzymes and of reactive oxygen species can activate or damage platelets and endothelial cells and impair some coagulation proteins. Activated platelets express P-selectin and tissue factor (TF) and release MPs. The increased expression of CD11b on the neutrophil surface allows the adhesion of neutrophils to endothelial cells and platelets and the assembly of coagulation proteases on the neutrophil surface. In addition, abnormalities in red blood cells (RBC), including biochemical changes in the cell membrane and content, may independently impair blood flow also through the formation of RBC aggregates. Furthermore, RBC aggregation facilitates the platelet and leukocyte interaction with the vessel wall. Tiziano Barbui et al. Blood 2013;122:2176-2184 ©2013 by American Society of Hematology

The prothrombotic effect of an elevated HCT in ET and PV patients. The prothrombotic effect of an elevated HCT in ET and PV patients. Elevated HCT can increase the thrombotic risk by multiple mechanisms: (1) it determines an increase in blood viscosity; (2) at high shear rates, the raise of red cell mass displaces platelets toward the vessel wall, thus facilitating shear-induced platelet activation and enhancing platelet–platelet interactions; (3) under the low shear rates, as in the venous bed, hyperviscosity can increase the thrombotic risk by causing a major disturbance to the blood flow; and (4) biochemical changes in cell membrane and intracellular content of red blood cells. Tiziano Barbui et al. Blood 2013;122:2176-2184 ©2013 by American Society of Hematology

Flow chart of the recommended treatment for patients with PV. Tiziano Barbui et al. Blood 2013;122:2176-2184 ©2013 by American Society of Hematology

Flow chart of the recommended treatment for patients with ET. Tiziano Barbui et al. Blood 2013;122:2176-2184 ©2013 by American Society of Hematology